Reactome | ESTG binds ESR1:chaperone complex

ESTG binds ESR1:chaperone complex

Stable Identifier

R-HSA-8939204

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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In the nucleus, estrogens bind to estrogen receptors, members of the nuclear receptor superfamily. Human cells have 2 estrogen receptors, ER alpha and ER beta, encoded by two genes. Expression of the two genes varies by tissue: both are expressed in the central nervous system, the cardiovascular system, the urogenital tract and in the breast and bone; ER alpha expression predominates in the uterus, mammary gland, and liver, and the gastrointestinal tract expresses only ER beta (Pearce and Jordan, 2004; Gustafsson et al, 1999; Pfaffl et al, 2001; reviewed in Bai and Gust, 2009). The receptors show 47% identity overall and share a common organization consisting of 6 domains: an N-terminal A/B domain with ligand-independent activation function, a C domain containing the 2 DNA-binding zinc fingers, a hinge region (D) with a nuclear localization signal, an E domain that contains the ligand binding and dimerization domains as well as a ligand-dependent transactivation function, and a C-terminal F domain of poorly characterized function. The DNA-binding domain is the most highly conserved (97% identity) while the ligand-bindind domain is more variable (47% identity) (reviewed in Ruff et al, 2000; Bai and Gust, 2009). ER alpha and beta can homo- and heterodimerize, and recognize a common estrogen-response element due to their shared DNA-binding domains (reviewed in Bai and Gust, 2009). Functional studies suggest that ER alpha and beta have overlapping but distinct roles in estrogen-responsive transcription (Harrington et al, 2003; Katzenellenbogen and Katzenellenbogen, 2000; Pearce and Jordan, 2004; Pfaffl et al, 2001)
In the unliganded state, estrogen receptors are part of a multi-subunit complex containing HSP90, p23 (also known as PTGES3) and other chaperone-associated proteins (Joab et al, 1984; Segnitz et al, 1995; Knoblauch et al, 1999; Bouhouche-Chatelier et al, 2001; Fliss et al, 2000; Oxelmart et al, 2006; reviewed in Smith and Toft, 2008; Bai and Gust, 2009). This complex is part of a chaperone binding and release cycle shared by many nuclear receptors (described in more detail in the pathway "HSP90 chaperone cycle for steroid hormone receptors") that governs receptor folding and activity and may contribute to a high-affinity conformation of the ligand-binding domain (reviewed in Pratt and Toft, 1997; Smith and Toft, 2008). HSP90 release from the receptor complex requires ATP hydrolysis (Smith et al, 1993; Grenert et al, 1997; Panaretou et al, 1998; Obermann et al, 1998; Smith et al, 1992; reviewed in Smith and Toft, 2008).

Literature References

PubMed ID	Title	Journal	Year
9295332	The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation Toft, DO, Mimnaugh, E, Fadden, P, Clark, J, Haystead, TA, Grenert, JP, Schulte, TW, Sausville, E, Krutzsch, H, Sullivan, WP, Ochel, HJ, Neckers, LM	J. Biol. Chem.	1997
9817749	In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis Russo, AA, Hartl, FU, Sondermann, H, Obermann, WM, Pavletich, NP	J. Cell Biol.	1998
10822011	Control of estrogen receptor ligand binding by Hsp90 Fliss, AE, Rao, J, Benzeno, S, Caplan, AJ	J. Steroid Biochem. Mol. Biol.	2000
11162936	Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology Katzenellenbogen, JA, Montano, M, Katzenellenbogen, BS, Choi, I, Sun, J, Ediger, TR, Weis, K, Delage-Mourroux, R, Martini, PG	J. Steroid Biochem. Mol. Biol.	2000
15094156	The biological role of estrogen receptors alpha and beta in cancer Jordan, VC, Pearce, ST	Crit. Rev. Oncol. Hematol.	2004
6201744	Common non-hormone binding component in non-transformed chick oviduct receptors of four steroid hormones Binart, N, Joab, I, Mester, J, Catelli, MG, Buchou, T, Radanyi, C, Baulieu, EE, Renoir, M	Nature	1984
18451092	Minireview: the intersection of steroid receptors with molecular chaperones: observations and questions Toft, DO, Smith, DF	Mol. Endocrinol.	2008
7892243	Subunit structure of the nonactivated human estrogen receptor Segnitz, B, Gehring, U	Proc. Natl. Acad. Sci. U.S.A.	1995
11250728	Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors Moras, D, Gangloff, M, Wurtz, JM, Ruff, M	Breast Cancer Res.	2000
9707442	ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo Roe, SM, Pearl, LH, O'Brien, R, Ladbury, JE, Prodromou, C, Panaretou, B, Piper, PW	EMBO J.	1998
9183567	Steroid receptor interactions with heat shock protein and immunophilin chaperones Toft, DO, Pratt, WB	Endocr. Rev.	1997
10588810	Estrogen receptor beta--a new dimension in estrogen mechanism of action Gustafsson, JA	J. Endocrinol.	1999
10207098	Role for Hsp90-associated cochaperone p23 in estrogen receptor signal transduction Knoblauch, R, Garabedian, MJ	Mol. Cell. Biol.	1999
16809759	The cochaperone p23 differentially regulates estrogen receptor target genes and promotes tumor cell adhesion and invasion Schneider, RJ, Garabedian, MJ, Braunstein, SE, Brooks, PC, Oxelmark, E, Roth, JM	Mol. Cell. Biol.	2006
19274700	Breast cancer, estrogen receptor and ligands Bai, Z, Gust, R	Arch. Pharm. (Weinheim)	2009
11795466	The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor Catelli, MG, Bouhouche-Chatelier, I, Chadli, A	Cell Stress Chaperones	2001
11478682	Tissue-specific expression pattern of estrogen receptors (ER): quantification of ER alpha and ER beta mRNA with real-time RT-PCR Meyer, HH, Pfaffl, MW, Daxenberger, A, Lange, IG	APMIS	2001
12943986	Activities of estrogen receptor alpha- and beta-selective ligands at diverse estrogen responsive gene sites mediating transactivation or transrepression Petz, LN, Katzenellenbogen, JA, Katzenellenbogen, BS, Harrington, WR, Sheng, S, Barnett, DH	Mol. Cell. Endocrinol.	2003